Case Report OPEN ACCESS Overexpression of linker for activated T cells, cyclooxygenase-2, CD1a, CD68 and myeloid/histiocyte antigen in an inflamed seborrheic keratosis

Abstract Context: Inflamed seborrheic keratoses are generally associated with the accumulation of variable numbers of lymphocytes and histiocytes in the superficial dermis. The precise immunologic mechanism of this histologic phenomenon is not known Case Report: A 62-year-old male presented with a patch on the right neck with additional features of inflammation. Skin biopsies for hematoxylin and eosin examination, as well as for immunohistochemistry analysis were performed. Results: H&E staining demonstrated classic features of an inflamed seborrheic keratosis. Overexpression of LAT, COX-2, CD1a, and CD68 was noticed in the inflammatory infiltrate. A strong presence of CD1a was also seen in the epidermis suprajacent to the inflammation. Myeloid/histiocyte antigen was strongly expressed by the keratinocytes. Conclusion: A complex immune response seems to be involved in the pathophysiology of an inflamed seborrheic keratosis

Immunologic findings in central centrifugal cicatricial alopecia

Introduction: Premature desquamation of the inner root sheath is described as a defining histologic feature of follicular degeneration syndrome/central centrifugal cicatricial alopecia; moreover, the immunological features of this disease are not well established.Case report: A 46-year-old African American female was evaluated for an asymptomatic scarring alopecia after using several chemicals on her hair. The clinical examination revealed visible, well defined patches of hair loss.Methods: Biopsies for hematoxylin and eosin examination, as well as for direct immunofluorescence and immunohistochemistry analysis were performed. We evaluated molecules involved in signaling of growth factor pathways (e.g. the Akts), specifically VEGF and Oct-4 to investigate involvement of these molecules in this disease. Hematoxylin and eosin staining demonstrated histopathologic findings of premature desquamation of the inner root sheath and eccentric thinning of the follicular epithelium, supporting the diagnosis of central centrifugal cicatricial alopecia. Direct immunofluorescence revealed strong depositions of IgG, Complement/C3 and fibrinogen around the multiple hair follicles and their supply vessels. Immunohistochemistry staining of the base of the hair follicle was seen with fibrinogen and Oct-4 antibodies. Immunohistochemistry also demonstrated increased expressions of VEGF around supply vessels of the hair follicle, as well as some overexpression of anti-human Akt-pS473 phosphorylation site specific antibody.Conclusions: Our immunologic findings suggest that the etiology of centrifugal cicatricial alopecia includes not only hair traction, but also a possible reactive immune response

LAT, EGFR -pY197, PCNL2, CDX2, HLA-DPDQDR, bromodeoxyuridine, JAM-A, and ezrin immunoreactants in a rubbed spongiotic dermatitis

Background: Acute and subacute spongiotic dermatitides are among the most commonly diagnosed types of dermatitis. Many patients rub their lesions, with the lesions becoming clinically thickened. The precise immunologic mechanisms within the thickening process are not well defined. Case report: An 85 year old male presented with the sudden clinical appearance of erythematous patches and small blisters on the back of his legs, with pruritis. Methods: Skin biopsies, one from a rubbed lesion and one from a non-rubbed lesion were submitted for hematoxylin and eosin (H&E), immunohistochemistry (IHC), and for direct immunofluorescence (DIF) analysis. Results: The H&E staining demonstrated classic features of a spongiotic dermatitis, but in the rubbed areas psoriasiform hyperplasia was also seen. The psoriasiform areas demonstrated positive, focal IHC staining with bromodeoxyuridine, LAT, EGFR-pY197, PCNL2, CDX2, and HLA-DPDQDR antibodies. DIF staining revealed positive staining of JAM-A and ezrin in the non-rubbed specimens in both the spongiotic epidermis and in the adjacent vessels; normal expression of these markers was appreciated in the rubbed biopsy. Conclusions: The immune response seems to be complex when a spongiotic dermatitis is converted from a non-rubbed to a rubbed lesion with histologic features of psoriasiform hyperplasia

Upregulation of anti-human ribosomal protein S6-p240, topoisomerase II ά, cyclin D1, Bcl-2 and anti-corneal antibodies in acute psoriasis

Background. The immunopathogenesis of psoriasis is complex, and involves alterations in the innate immunologic system Case Report: A 57-year-old female was evaluated for the presence of rapidly appearing plaques on the knees and elbows. Methods: Skin biopsies for hematoxylin and eosin examination, as well as for direct immunofluorescence and immunohistochemistry analysis were performed. Results: H&E examination demonstrated classic features of psoriasis. Direct immunofluorescence revealed positive anti-corneal antibodies with several immunoglobulins, as well as positivity to upper and deep small dermal blood vessels. Immunohistochemistry revealed an increased expression of survivin, anti-human-ribosomal protein S6-p240, Topoisomerase II ά, cyclin D1, and Bcl-2 in lesional plaques. Conclusions: The pathobiology of psoriasis seems to involve a series of molecules involved in a complex interaction between the inflammation itself, cell cycle regulation, and ectopic expression of selected molecules

Presence of neutrophil extracellular traps and antineutrophil cytoplasmic antibodies associated with vasculitides

Abstract Context: Anti-neutrophil p-ANCA antibodies are directed against antigens in the peripheral cytoplasm of both neutrophilic granulocytes and monocytes. They are detected in several autoimmune disorders and are particularly associated with systemic vasculitis. Case Report: We report a case of a 54-year-old female presenting with a pruritic rash, including purpura and diffuse erythema. A biopsy with hematoxylin and eosin (H & E) analysis, direct immunofluorescence (DIF), immunohistochemistry (IHC) and enzyme-linked immunosorbent assays for ANCAs were performed. The H & E staining demonstrated leukocytoclastic vasculitis, with focal vascular fibrinoid necrosis. The DIF revealed evidence of vasculitis, the presence of p-ANCAs and neutrophil extracellular traps (NETs). The IHC displayed autoreactivity to myeloperoxidase within the vessels. The IHC aided in ruling out any intrinsic autofluorescence of the vessels. Conclusions: By observing the deposition of neutrophil extracellular traps and myeloperoxidase in inflamed skin vessels, biopsy analysis may alert physicians for rapid therapeutic intervention in patients presenting with possible vasculitides

MAST CELLS, MAST/STEM CELL GROWTH FACTOR RECEPTOR (C-KIT/CD117) AND IGE MAY BE INTEGRAL TO THE PATHOGENESIS OF ENDEMIC PEMPHIGUS FOLIACEUS

Introduction: Pemphigus foliaceus (PF) is endemic in some South American countries, especially in Colombia and Brazil; in Brazil, it is also known as fogo selvagem (FS). We aimed to study the presence of mast cells and the expression of the mast/stem cell growth factor receptor (c-kit/CD117) in PF skin biopsies, as well as the role of IgE in the disease pathogenesis. Methods: Forty-four skin biopsies from patients affected by endemic PF (EPF) (30 patients from El Bagre, Colombia, and 14 from the northeastern region of São Paulo State, Brazil), 48 control biopsies from Colombian and Brazilian endemic areas, and additional control biopsies from none endemic areas in Colombia and the USA non were studied. Immunohistochemistry (IHC) was performed to evaluate skin biopsies with anti-mast cell tryptase (MCT), anti-c-kit and anti-IgE antibodies. We also searched for serum IgE in 30 EPF and 30 non-atopic controls from the El Bagre region via ELISA. In our El Bagre patients and controls, we also searched for IgE in skin samples by direct immunofluorescence. Results: In 100% of the EPF biopsies, MCT, c-kit and IgE were identified with stronger expression relative to control biopsies, especially in the inflammatory infiltrates around upper dermal blood vessels and dermal eccrine glands. IgE staining was positive along the BMZ in some EPF skin samples. The DIF results confirmed a linear deposition of IgE at the BMZ. Increased IgE serum levels were also noted in PF patients relative to controls.. Conclusions: In patients with EPF, the observed increased expression of MCT, c-kit and IgE in lesional skin, associated with higher serum IgE levels may indicate possible IgE participation in the antigenic response

IMMUNOHISTOCHEMISTRY STUDIES IN A CASE OF DERMATITIS HERPETIFORMIS DEMONSTRATE COMPLEX PATTERNS OF REACTIVITY

Introduction: Dermatitis herpetiformis (DH) is an autoimmune, clinically pleomorphic, papulovesicular disorder sometimes associated with celiac disease and gluten sensitivity. DH is categorized by subepidermal vesicles and bullae on hematoxylin and eosin (H&E) staining, and with immunoglobulin A deposits present along the dermal papillary tips on direct immunofluorescence (DIF). Case Report: We describe a 50 year old female that presented with sudden onset pruritus and clinical blisters, predominantly on extensor areas of the extremities. Biopsies for H&E examination, as well as immunohistochemistry (IHC) and DIF analysis were performed. Results: H&E examination demonstrated subepidermal blistering; within the blister lumen, numerous neutrophils were present, with occasional eosinophils and lymphocytes also seen. DIF examination revealed linear deposits of IgA along the epidermal basement membrane zone, associated with other immunoglobulins and complement. IHC examination showed similar patterns of reactivity to IgA, and also to other immunoreactants. Cells positive for CD1a were present within the blisters, correlating with S-100 staining. Cells staining positive for CD8, CD45 and occasionally CD4 and Granzyme B were seen not only in the blister lumens, but also around neurovascular packages under the blisters. Finally, CD2 positive cells were found around the upper dermal blood vessels. Discussion: Focal DIF linear IgA deposition is the classic hallmark diagnostic finding in DH. However, it is possible that genetic susceptibility and environmental triggers also play a crucial role in the pathogenesis, often acting via cellular pathways exhibiting disease-associated polymorphisms. In tolerance breakthrough, the initiating antigen presenting cells likely lead to immune system cell differentiation, and activation of adaptive immunity

Survivin, p53, MAC, Complement/C3, fibrinogen and HLA-ABC within hair follicles in central and centrifugal cicatricial alopecia

Abstract Context: Central centrifugal cicatricial alopecia (CCCA; originally entitled follicular degeneration syndrome, or hot comb alopecia) was first described in African American women utilizing hot combs and/or strong chemical hair care products. Case Report: A 67 year old African American female was evaluated for the presence of alopecic areas occurring on the scalp vertex, and spreading centrifugally. The alopecic lesions appeared as diffuse patches, including atrophic small areas surrounding individual hair follicles. Patients and Methods: Skin biopsies for hematoxylin and eosin examination, as well as for direct immunofluorescence and immunohistochemistry analyses were performed. Results: hematoxylin and eosin staining demonstrated histopathologic findings of premature desquamation of the inner root sheath and eccentric thinning of the follicular epithelium, supporting the diagnosis of CCCA. Direct immunofluorescence revealed strong depositions of Complement/C3, fibrinogen and kappa light chains around the hair follicles. Immunohistochemistry demonstrated increased expressions of HLA-ABC (as in African American patients with insulin independent diabetes mellitus). We also detected positive p53, bcl-2 and MAC staining in the hair follicle areas. Conclusions: Follicular degeneration syndrome may have an important immunological component previously not described, and multicolor immunofluorescence may be useful in establishing an early diagnosis